Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline.
Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.
Churchill
P C
PC
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Rossi
N F
NF
Churchill
M C
MC
Bidani
A K
AK
McDonald
F D
FD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000097:blood; D013806:Theophylline / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D003524:Cyclosporins; D012964:Sodium; D013806:Theophylline; D011188:Potassium; D010130:p-Aminohippuric Acid